Bioengineering & Translational Medicine最新文献

{"title":"An osteogenesis mimicking biomineralized bone adhesive for rapid skeletal regeneration","authors":"Yuqi Liu, Hao Luo, Bin Guo, Xiangming Chen, Martin J. Stoddart, Wen Chen, Xucheng Yang, Yong Zhu, Jianxi Zhu","doi":"10.1002/btm2.70182","DOIUrl":"https://doi.org/10.1002/btm2.70182","url":null,"abstract":"Osteogenesis is a crucial process in bone injury repair where osteoblasts mineralize collagen to form new bone at the fracture site. For effective bone regeneration in comminuted fractures, it is essential to develop an osteogenic bone adhesive that can be applied at the time of fixation to temporarily immobilize fragmented bone pieces. We present a flowable, injectable adhesive that enables on‐demand bonding of irregular fracture surfaces and, after photocuring, provides enhanced mechanical integrity while supporting osteogenesis. To meet these clinical requirements, we engineered a gelatin methacryloyl–polyethylene glycol diacrylate (GelMA–PEGDA) network bone adhesive that undergoes rapid photocuring to enable on‐demand bonding and immediate mechanical stabilization at the fracture site. By incorporating nanoscale hydroxyapatite (nHA) to confer a bone‐mineral‐mimetic composition and biomineralization capacity, the photocured adhesive promotes bone marrow‐derived mesenchymal stem cell recruitment and supports skeletal regeneration. During degradation, the organic–inorganic phase of the adhesive can guide osteogenesis, leading to satisfactory healing outcomes in fractures. Overall, the compositional and mechanical biomimicry, photosensitivity and osteogenic potential of GelMA–nHA–PEGDA render it a potential all‐in‐one solution for minimally invasive treatment of multiple skeletal diseases.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"8 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endovascular magnetic filters for removing excess chemotherapeutic drugs from blood flow using dimensionless scaling laws","authors":"Won‐Seok Heo, Steven W. Hetts, Vitaliy L. Rayz","doi":"10.1002/btm2.70151","DOIUrl":"https://doi.org/10.1002/btm2.70151","url":null,"abstract":"Intra‐arterial chemotherapy (IAC) for hepatocellular carcinoma (HCC) is limited by the escape of chemotherapeutic agents into systemic circulation, causing severe side effects such as heart failure. This study aims to develop and optimize endovascular magnetic filtration devices to enhance IAC efficacy, by targeted removal of excess drug‐coated ultrasmall superparamagnetic iron oxide (USPIO) particles from circulation. Device performance was evaluated through multi‐physics simulations that coupled the transport of drug‐coated magnetic particles in blood flow with magnetic interactions and magnetophoretic forces. A dimensional analysis framework was applied to characterize particle capture efficiency () across alternative device designs, and numerical predictions were compared with published benchtop experiments. Optimized multi‐stage filters achieved up to ~80% predicted capture efficiency, while reducing the risk of intravascular device collapse. These results demonstrate a novel strategy for reducing systemic toxicity in IAC through endovascular magnetic filtration, indicating its potential to improve the safety and effectiveness of HCC treatment.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"25 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and determinants of mRNA Lipid Nanoparticle biodistribution: From pharmacokinetics to clinical translation","authors":"Zakia Alhareth, César López‐Camacho","doi":"10.1002/btm2.70183","DOIUrl":"https://doi.org/10.1002/btm2.70183","url":null,"abstract":"Messenger RNA (mRNA) therapeutics formulated in lipid nanoparticles (LNPs) have transformed the field of nucleic acid medicine by enabling transient, programmable protein expression for vaccination, protein replacement, immunotherapy, and genome engineering. Extending their clinical success beyond vaccines requires a mechanistic understanding of where LNP components and mRNA travel, which cells they enter, where cargo is translated, and how each component is cleared. Such biodistribution outcomes are governed by a complex interplay between nanoparticle physicochemical properties, administration route, protein corona formation, host physiology, intracellular trafficking, and degradation. Importantly, the biodistribution of lipid components, intact mRNA, degraded RNA fragments, and translated proteins represents distinct yet interconnected biological processes that should not be interpreted interchangeably. Advances in molecular imaging, quantitative nucleic acid analysis, mass spectrometry, spatial and single‐cell technologies, and pharmacokinetic modeling are improving their resolution across tissues and time. In parallel, rational lipid engineering, selective organ targeting, biodegradable ionizable lipids, ligand‐directed delivery, and artificial intelligence‐assisted design are expanding opportunities for tissue‐specific delivery beyond the liver and lymphoid organs. However, interpretation remains constrained by assay heterogeneity, incomplete understanding of protein corona dynamics and endosomal escape, species‐dependent differences, and the absence of harmonized regulatory standards. This review examines the mechanisms governing mRNA‐LNP disposition, evaluates what current analytical methods detect and miss, synthesizes preclinical and clinical evidence, and considers the strategies needed to achieve predictable, tissue‐selective, and clinically translatable mRNA delivery.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"7 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical fingerprints in breast cancer research: A multimodal experimental approach","authors":"Federica Banche-Niclot,&nbsp;Rosalia Ferraro,&nbsp;Valerio Di Palo,&nbsp;Paola de Paolis,&nbsp;Francesca Taraballi,&nbsp;Sergio Caserta","doi":"10.1002/btm2.70148","DOIUrl":"https://doi.org/10.1002/btm2.70148","url":null,"abstract":"<p>Breast cancer remains the leading cause of cancer-related mortality among women worldwide. Tumor biomechanics are not merely a symptom: they represent a functional signature with translational relevance in diagnostic, prognostic, and therapeutic resistance. Despite this, few experimental models are engineered to systematically investigate these physical properties across biological systems. Here, this study presents a multimodal biomechanical platform combining engineered 3D breast cancer spheroids with <i>ex vivo</i> tissue analysis to profile and compare viscoelastic behavior of healthy and tumoral environments. Rheometry and compression testing revealed a consistent mechanical shift in tumor-derived samples marked by increased stiffness and force-dependent nonlinear behavior, mirroring the ECM remodeling typical of aggressive phenotypes. This increased rigidity may adversely affect chemotherapy effectiveness by hindering drug delivery and altering cellular mechanotransduction. These biomechanical fingerprints enable quantitative discrimination between healthy and cancerous tissues and can serve as a surrogate marker of malignancy. By supporting the development of mechanics-informed diagnostic tools, our platform offers a reproducible, clinically relevant framework to integrate biomechanical screening into translational breast cancer pipelines.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"11 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative myeloid ecotropic viral integration site 1-engineered exosome platform combating oxidative stress and inflammation in acute pulmonary damage","authors":"Yukun Zhang,&nbsp;Ke Pang,&nbsp;Zefa Ling,&nbsp;Shouyong Wang,&nbsp;Bo Hu,&nbsp;Surong Deng,&nbsp;Zhao Yang","doi":"10.1002/btm2.70150","DOIUrl":"https://doi.org/10.1002/btm2.70150","url":null,"abstract":"<p>Phosgene-induced acute lung injury (P-ALI) remains a severe clinical challenge due to the absence of targeted therapies. In this study, we developed a novel therapeutic strategy based on myeloid ecotropic viral integration site 1-engineered exosomes loaded with curcumin (Meis1-Exo@Cur). This nanotherapeutic platform exhibited potent protective effects in both cellular and animal models of P-ALI, significantly reducing inflammation, oxidative stress, and apoptosis while promoting tissue repair. Mechanistically, Meis1-Exo@Cur exerted its therapeutic effects through coordinated inhibition of the nuclear factor kappa-B/mitogen-activated protein kinase signaling pathways and activation of the Nrf2/HO-1 pathway, accompanied by remodeling of the immune microenvironment. These findings identify Meis1-Exo@Cur as a promising therapeutic candidate for P-ALI and provide a potential framework for exosome-based precision therapy in inflammatory lung diseases.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"11 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focal therapeutic conditions matter: How energy affects antigen presentation and T cell activation","authors":"Minhan Jiang,&nbsp;Qi Shao,&nbsp;Joseph Vallin,&nbsp;Yoji Shimizu,&nbsp;Brandon Burbach,&nbsp;Samira Azarin,&nbsp;John Bischof","doi":"10.1002/btm2.70152","DOIUrl":"https://doi.org/10.1002/btm2.70152","url":null,"abstract":"<p>Energy-based minimally invasive cancer focal therapies (FTs), including thermal ablation (Heat), cryoablation (Cryo), and irreversible electroporation (IRE), can induce immunomodulatory effects and can synergize with immunotherapy to engage the immune system for systemic and long-term antitumor response. However, the immunogenicity of each FT can vary based on treatment specifics, and the mechanisms underlying these differences are not fully understood. We employed a model antigen (ovalbumin, OVA) and an in vitro platform to investigate the upstream processing steps that initiate immune priming. This platform enabled quantitative assessment of antigen release, antigen presentation, dendritic cell (DC) activation, antigen-specific T cell proliferation and the generation of damage-associated molecular patterns (DAMPs), cytokines and chemokines. Both antigen-specific signaling and T cell response are highly dependent on the focal therapeutic conditions applied to the cancer cells. Cryo resulted in the highest release of protein, OVA antigen, ATP, and HMGB1, followed by IRE and Heat. Despite not yielding the most antigen, IRE-treated B16-OVA elicited the most DC activation and OVA-specific T cell proliferation. Dose–response analysis using OVA protein and SIINFEKL peptide confirmed a positive correlation between antigen availability and T cell response. We also observed substantial adjuvant effects that enhance the immune processing and T cell response by stimulus in cell lysates independently of antigen quantity. Specifically, IRE-treated B16 cell lysates induced the most significant improvement in dendritic cell (DC) activation and T cell proliferation compared to Heat and Cryo when paired with equal amounts of antigen. Our findings position IRE as the most immunogenic FT condition in our system. This study highlights the critical interplay between antigen release, adjuvant signals, and immune processing in shaping FT-driven antitumor immunity.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"11 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical-medical convergence in heart failure: Artificial intelligence, finite-element modeling, and 3D printing for diagnosis and prognosis","authors":"Quazi Noor E Sabrina,&nbsp;Quazi Md Zobaer Shah,&nbsp;Quazi Noor E Sohela,&nbsp;Md Mahabub Hasan Mousum,&nbsp;Md. Moyeen Uddin Chisty,&nbsp;Quazi Md. Akbar Shah","doi":"10.1002/btm2.70156","DOIUrl":"10.1002/btm2.70156","url":null,"abstract":"<p>Heart failure remains a leading cause of global morbidity and mortality, yet routine clinical indices often miss the regional biomechanical disturbances that drive progression and shape treatment response. This State-of-the-Art review examines how finite-element (FE) modeling, additive manufacturing, and artificial intelligence (AI) are converging to improve the diagnosis, phenotyping, procedural planning, and prognostic assessment of heart failure (HF). Although these technologies have matured in structural heart disease and transcatheter intervention research, their greatest translational potential may lie in HF, where patient-specific ventricular remodeling, myocardial stress–strain heterogeneity, valve-ventricular coupling, and device-tissue interaction are incompletely captured by conventional clinical indices. We synthesize translational and clinical literature published from 2015 to 2026 on imaging-derived FE models, multimaterial 3D-printed cardiovascular phantoms, and AI-based analytic pipelines relevant to HF populations or HF-related decision pathways. FE approaches provide mechanistic estimates of regional myocardial deformation, wall stress, and remodeling trajectories; 3D-printed phantoms enable bench-top validation, device rehearsal, and hemodynamic replication; and AI supports segmentation, phenotyping, multimodal integration, and risk prediction. Across all three domains, however, the evidence base remains dominated by retrospective studies, bench validation, and small translational cohorts, with limited prospective outcome validation and inconsistent reporting of reproducibility. We therefore propose an evidence-aware, HF-centered framework for integrating computational mechanics, physical phantoms, and data-driven models into digital-physical twin workflows. From a clinical perspective, the near-term opportunity is not autonomous decision-making, but better mechanistic phenotyping, more transparent procedural planning, and more rigorous testing of patient-specific hypotheses before intervention. Standardized reporting, external validation, careful materials characterization, and multicenter endpoint-linked studies will be essential for clinical translation.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"11 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148286792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapamycin-nanoliposomes target the mTORC1-mediated autophagy–lysosomal and NLRP3/Caspase-1 pathways to inhibit nucleus pulposus cell senescence in intervertebral discs","authors":"Hui Xing,&nbsp;Miao Yu,&nbsp;Jiabin Liu,&nbsp;Runzhi Zhao,&nbsp;Xuezheng Ai,&nbsp;Rong Tang,&nbsp;Tong Zhu,&nbsp;Yuqing Li,&nbsp;Lu Jiang,&nbsp;Quanfang Wei,&nbsp;Youying Huang,&nbsp;Yu Guo,&nbsp;Tao Jiang,&nbsp;Bo Huang","doi":"10.1002/btm2.70165","DOIUrl":"10.1002/btm2.70165","url":null,"abstract":"<p>Nucleus pulposus (NP) cell quiescence maintains intervertebral disc homeostasis, while mTORC1 regulates autophagy–lysosomal function and inflammatory secretion to preserve quiescence—rapamycin specifically targets mTORC1. Herein, we fabricated rapamycin-nanoliposomes (rapa-lipos) via ultrasonic dispersion, thin-film dispersion, and filtration to improve rapamycin bioavailability, investigating their role in inhibiting the senescence phenotype of NP cells through <i>β</i>-gal staining, lysosomal staining, transmission electron microscopy, ELISA, and cell cycle inhibitors. The mechanistic effects of rapa-lipos on mTORC1, NLRP3/Caspase-1 pathway (NCP) and autophagy–lysosomal pathway (ALP) were also analyzed by western blotting, immunofluorescence (IF), Si-RNA (raptor), and PCR. In vivo, rapa-lipos were injected into rat intervertebral disc with IL-1<i>β</i>-induced degeneration, assessed via HE staining, x-ray, MRI, and IF. Rapa-lipos exhibited high encapsulation efficiency, favorable drug loading, uniform particle size, and controlled release, suppressing NP cell senescence-related phenotypes (morphological changes, elevated IL-1β/TNF-<i>α</i> secretion, increased <i>β</i>-gal activity, lysosomal dysfunction, upregulated P21/P16 and reduced P27 expression). Mechanistically, rapa-lipos targeted-inhibited mTORC1, then blocked NCP and activated ALP to maintain NP cell quiescence. In vivo, x-ray, MRI and histological evaluation confirmed rapa-lipos mitigated intervertebral disc degeneration. Collectively, rapa-lipos target mTORC1-mediated NCP and ALP to inhibit NP cell senescence, offering a promising strategy for intervertebral disc degeneration prevention.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"11 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring vascular changes in renal fibrosis in mice using multimodal optical and ultrasonic imaging","authors":"Ruijing Zhang,&nbsp;Yuhang Zhang,&nbsp;Chuanlong Lu,&nbsp;Keyi Fan,&nbsp;Heng Wang,&nbsp;Qian Wang,&nbsp;Yijie Ning,&nbsp;Yaling Li,&nbsp;Zeyu Zhang,&nbsp;Xiaohua Jia,&nbsp;Honglin Dong","doi":"10.1002/btm2.70169","DOIUrl":"10.1002/btm2.70169","url":null,"abstract":"<p>Chronic kidney disease (CKD) has become one of the major diseases threatening global health, with its increasing incidence and mortality rates. Early identification of chronic kidney disease is crucial for accurate disease staging, timely intervention, and improved prognosis. However, the commonly used clinical diagnostic indicators, such as creatinine, albumin level and glomerular filtration rate, can only identify advanced CKD. Imaging examinations, such as computed tomography and magnetic resonance imaging, have limitations such as high costs and high risk of complications, and are not suitable for large-scale screening of high-risk populations. Renal biopsy is the gold standard for diagnosing renal fibrosis, but it is invasive. Previous studies have shown that capillary rarefaction is an early event of renal fibrosis, occurring earlier than tubular atrophy and interstitial collagen deposition. However, there is a lack of a minimally invasive, low-cost, high-resolution, dynamic and real-time monitoring method for renal microcirculation that is suitable for large-scale screening. There is an urgent need for reliable methods to screen early-stage CKD patients. In this study, we have for the first time combined real-time and wide-field laser speckle imaging (RFLSI), near-infrared II imaging (NIR-II), duplex ultrasound (DUS) and Contrast-Enhanced Ultrasound (CEUS) to monitor vascular changes and evaluate the progression of renal fibrosis. The combination of four imaging methods enabled the early monitoring of CKD progression by monitoring microcirculation. Among them, CEUS can detect changes in the renal microcirculation at the early stage of renal fibrosis, even earlier than the pathological damage of the kidneys. Through visualization and quantification of the progression of renal fibrosis and validation through histopathology, this study utilizes preclinical imaging to supplement clinical imaging of renal fibrosis, providing a more comprehensive method for monitoring microcirculation, which is helpful for guiding clinical decisions and providing insights into disease progression.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"11 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered exosomes with RNA-motif short hairpin RNA loading and Rab4-boosted production enable controlled ferroptosis in endometrial carcinoma","authors":"Jiarui Zhang,&nbsp;Yuwei Yao,&nbsp;Wan Shu,&nbsp;Shuangshuang Cheng,&nbsp;Guanglei Zhong,&nbsp;Jia Yu,&nbsp;Jinhua Chen,&nbsp;Kejun Dong,&nbsp;Yingying Peng,&nbsp;Jun Zhang,&nbsp;Hongbo Wang","doi":"10.1002/btm2.70163","DOIUrl":"10.1002/btm2.70163","url":null,"abstract":"<p>Therapeutic challenges in endometrial carcinoma (EC) arise from the limited efficacy and toxicity of current treatments. Although exosome-based RNA interference shows promise, its clinical translation is hindered by inefficient cargo loading, low yields, and poor tumor targeting. We have engineered an exosome platform (cRGD-ExoM) that integrates the following innovations: Firstly, RNA motifs enable the enrichment of shRNA loading by over 80-fold for targeting of ferroptosis regulators (glutathione peroxidase 4/ferroptosis suppressor protein 1/ferritin heavy chain [GPX4/FSP1/FTH]). Secondly, Rab4 silencing amplifies exosome biogenesis via dysregulated endosomal recycling, enhancing tumor cell uptake by impairing endosome maturation—a dual-action mechanism that boosts both production and delivery. Thirdly, cRGD peptides confer αvβ3-integrin-specific targeting. cRGD-ExoM induces potent ferroptosis by increasing lipid peroxidation and downregulating GPX4/FSP1/FTH, significantly suppressing EC tumor growth in vivo without causing systemic toxicity. The platform's modular design allows for spatiotemporal control of loading, production, and targeting, demonstrating its scalability. This study provides new insights into the precision treatment of endometrial cancer by developing engineered, multifunctional, exosome-based therapeutic drugs that combine mechanism precision and translational feasibility in tumor treatment.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"11 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}